LY-364947

SKU: orb1306643

Description

LY-364947 (HTS466284) is a selective, ATP-competitive small molecule inhibitor targeting the TGF-β type I receptor kinase (ALK5). It is widely utilized in biochemical and cellular assays to investigate TGF-β signaling pathways in cancer, fibrosis, and developmental biology research, demonstrating activity in both in vitro and in vivo models.

Research Area

Cell Biology, Metabolism Research, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 396129-53-6
• MW: 272.3
• Purity: 99.96% (May vary between batches)
• Formula: C₁₇H₁₂N₄
• SMILES: N1C=C(C(=N1)C1=NC=CC=C1)C1=CC=NC2=CC=CC=C12
• Target: TGF-beta/Smad,MLK,RIP kinase,Casein Kinase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (3.67 mM);DMSO:7.5 mg/mL (27.54 mM)

Bioactivity

• Target IC50:
  RIPK2:0.11 μM|TGFβRII:0.4 μM|MLK7K:1.4 μM|CK1δ:0.22 μM|TGFβRI:59 nM
• In Vivo:
  At a concentration as low as 0.25 μM, LY364947 enhances the xVent2-lux BMP4 response in NMuMG cells by 30%. At 2 μM, it prevents TGF-β-induced epithelial-mesenchymal transition (EMT) in NMuMG cells. A 3 μM dose of LY364947, after 24 hours of treatment, induces the expression of Prox1 and LYVE-1 in nearly all HDLECs. LY364947 promotes the nuclear export of Foxo3a and is characterized by low Smad2/3 and high Akt phosphorylation levels in leukemia-positive cells. When co-cultured with OP-9 stromal cells, LY364947 (at concentrations <20 μM) inhibits the colony-forming ability of leukemia-initiating cells. Acting as an ATP-competitive, tight-binding inhibitor, LY364947 inhibits P-Smad3 phosphorylation through TGFβR-I kinase with a Ki of 28 nM and inhibits Smad2 phosphorylation in NMuMG cells in vivo with an IC50 of 135 nM.
• In Vitro:
  Administering 1 mg/kg i.p. of LY364947 significantly enhances the LYVE-1-positive regions within the tumor tissues in a BxPC3 pancreatic cancer xenograft model. Similarly, 25 mg/kg i.p. of LY364947 markedly increases LYVE-1-positive areas in a chronic peritonitis mouse model, indicating accelerated lymphangiogenesis. Additionally, LY364947 (25 mg/kg) increases p-Akt levels and decreases nuclear Foxo3a in leukemia-initiating cells in mice infected with CML.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CK1δ, Casein Kinase, CaseinKinase, Inhibitor, HTS 466284, HTS466284, HTS-466284, LY 364947, LY364947, LY-364947, inhibit, MLK-7K, Smad, RIPkinase, RIP kinase, RIPK2, Transforming growth factor beta receptors, TGFbeta/Smad, TGFβ, TGF-β Receptor, TGF-β/Smad, TGFβRI, TGFβRII, TGFb, TGF-b/Smad, TGFbeta, TGF-beta

Compound Identifiers

PubChem CID

447966